Dr. Anne Cappola, who trained in Endocrinology at the Massachusetts General Hospital and the Johns Hopkins Hospital, recently completed an Sc.M. in Epidemiology at the Johns Hopkins School of Public Health and a fellowship at the Johns Hopkins Center on Aging and Health. In April, 2001, Dr. Cappola joined the faculty at the University of Maryland as Assistant Professor of Medicine and Epidemiology. She has strong mentor ship from Dr. Alan Shuldiner, an endocrinologist with expertise in aging, and Dr. Linda Fried, a geriatrician and epidemiologist renowned for her work on frailty. They will provide her with extensive resources and a stimulating interdisciplinary environment to launch her independent academic career. Sarcopenia, the involuntary loss of skeletal muscle mass and function, is a potentially modifiable condition that contributes to frailty, functional dependence, and falls in older individuals. The role of the endocrine system in the development of sarcopenia is poorly understood. The central goal of this proposal is to define the role of androgens and myostatin in sarcopenia in older women through examination of epidemiologic and molecular data. In Specific Aim 1, Dr. Cappola proposes to characterize the distribution of ovarian and adrenal androgens and myostatin in a random sample of women over the age of 65 using banked blood from the Cardiovascular Health Study (CHS). In Specific Aim 2, she will perform analyses to determine whether lower or declining levels of androgens and/or higher or increasing levels of myostatin are independently associated with sarcopenia in CHS and in a cohort of women with relatively high function, the Women?s Health and Aging Study II. In Specific Aim 3, she will perform a pilot study of low-dose testosterone in androgen-deficient older women to evaluate the safety and efficacy of this intervention and to delineate the molecular mechanisms whereby androgens mediate changes in muscle using functional genomics approaches. Dr. Cappola?s interdisciplinary training, strong mentor ship, carefully designed career development program, supportive environment, and novel research plan will give her the experience and tools she needs to develop into a highly successful, independent clinical investigator.